The present invention relates to the use of purine nucleoside analogs in the treatment of viral infections. More particularly, the present invention relates to the use of certain substituted pyrrolo[2,3-d]pyrimidine nucleosides against human immunodeficiency virus (HIV-1), human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1).
The antiviral activity of pyrrolo[2,3-d]pyrimidine nucleosides such as tubercidin, toyocamycin and sangivamycin and some substituted derivatives has been previously documented. Bergstrom, et al., "Antiviral Activity of C-5 Substituted Tubercidin Analogs," J. Med. Chem. (1984), Vol. 27, pp. 285-292; DeClercq, et al., "Antirhinovirus Activity of Purine Nucleoside Analogs," Antimicrobial Agents and Chemotherapy (1986), Vol. 29, No. 3, pp. 482-487. These compounds are particularly attractive as potential antiviral agents because of their stability to deamination by adenosine deaminase and glycosidic bond cleavage by purine nucleoside phosphorylases, the two major pathways of purine nucleoside inactivation.
However, although certain previously described pyrrolo[2,3-d] pyrimidine nucleosides have been reported as potently antiviral, their clinical usefulness is limited because they also exhibit unacceptable levels of cytotoxicity. It would thus be highly advantageous to find derivatives of these compounds which have decreased cytotoxicity but retain their antiviral activity, particularly against viruses which are currently of major concern such as the human immunodeficiency and herpes viruses.
The present invention relates to a class of substituted pyrrolo[2,3-d]pyrimidine nucleosides which exhibit antiviral activity, particularly against HIV-1, HCMV and HSV-1, and whose levels of cytotoxicity are significantly lower than their parent compounds.